CREATINE KINASE AND ENERGY METABOLISM HOMEOSTASIS

肌酸激酶和能量代谢稳态

基本信息

  • 批准号:
    2459870
  • 负责人:
  • 金额:
    $ 8.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1995
  • 资助国家:
    美国
  • 起止时间:
    1995-08-01 至 2000-07-31
  • 项目状态:
    已结题

项目摘要

The Research: Energy storage, maintenance and utilization is critical to cellular and muscle function. It has been thought that creatine kinase plays a crucial role in this process by providing an "energy reserve" function, however the compensatory mechanisms and molecular responses to deficiencies of the creatine kinase system are incompletely understood. Based on the traditional understanding of the creatine kinase system one would expect that animals lacking M creatine kinase would be severely impaired or unable to survive. Surprisingly, recent studies of cardiac and skeletal muscle of mice which express no M creatine kinase, demonstrate no noticeable abnormalities at rest, or under conditions of low ATP flux, suggesting that this is not flee case. When a heart from one of these mice is subjected to acute isoproterenol infusion (high ATP flux), there appears to be an "uncoupling" of ATP and creatine phosphate. The hypothesis of this proposal is that M creatine kinase activity is of crucial importance in maintaining myocardial energy metabolism homeostasis in high flux stress states. The applicant has developed an isolated perfused mouse heart preparation, to which he will apply a multidisciplinary approach integrating sophisticated biochemical techniques (31P NMR spectroscopy), physiologic and molecular techniques to study the following Specific Aims: l) Are concentrations of ATP and creatine phosphate uncoupled in hearts from M creatine kinase homozygous knockout mice under high flux but not under low flux stress? 2) Can the coupling of ATP to creatine phosphate concentrations in muscle cells subjected to low and high flux stress be altered by the over-expression of creatine kinase isoenzymes or of the creatine transporter? 3) Does the absence of functional M creatine kinase alter the expression of other genes as a compensatory mechanism in M creatine kinase homozygous knockout mouse hearts under basal conditions and under conditions of low and high flux stress?
研究:能源储存、维护和利用对于 细胞和肌肉功能。人们认为肌酸激酶 在这一过程中起着至关重要的作用,提供了“能源储备”, 功能,然而,补偿机制和分子反应, 肌酸激酶系统的缺陷还不完全清楚。 基于对肌酸激酶系统的传统认识, 我认为缺乏M肌酸激酶的动物会严重地 受损或不能生存。令人惊讶的是,最近的心脏和 不表达M肌酸激酶小鼠的骨骼肌,证明不 静息时或低ATP通量条件下的明显异常, 这说明这不是一起逃逸案当这些老鼠的心脏 进行急性异丙肾上腺素输注(高ATP通量), 似乎是ATP和磷酸肌酸的“解偶联”。的 这一建议假设是,M肌酸激酶活性是 在维持心肌能量代谢稳态中至关重要 在高通量应力状态下。申请人已经开发了一种分离的 灌注的小鼠心脏准备,他将应用于 多学科方法整合复杂的生物化学 技术(31P NMR光谱),生理和分子技术, 研究以下具体目标:l)是ATP浓度和 肌酸激酶纯合子心肌磷酸肌酸解偶联 基因敲除小鼠在高通量下,而不是在低通量压力下?2)能否 肌细胞中ATP与磷酸肌酸浓度的偶联 受到低和高通量应力被改变过表达的 肌酸激酶同工酶或肌酸转运蛋白?3)是否 功能性M肌酸激酶的缺乏改变了其他 肌酸激酶M基因纯合敲除的补偿机制 在基础条件下和在低和高条件下的小鼠心脏 通量应力?

项目成果

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HOWARD D WEINBERGER其他文献

HOWARD D WEINBERGER的其他文献

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{{ truncateString('HOWARD D WEINBERGER', 18)}}的其他基金

CREATINE KINASE AND ENERGY METABOLISM HOMEOSTASIS
肌酸激酶和能量代谢稳态
  • 批准号:
    6043659
  • 财政年份:
    1995
  • 资助金额:
    $ 8.36万
  • 项目类别:
CREATINE KINASE AND ENERGY METABOLISM HOMEOSTASIS
肌酸激酶和能量代谢稳态
  • 批准号:
    2211584
  • 财政年份:
    1995
  • 资助金额:
    $ 8.36万
  • 项目类别:
CREATINE KINASE AND ENERGY METABOLISM HOMEOSTASIS
肌酸激酶和能量代谢稳态
  • 批准号:
    2211583
  • 财政年份:
    1995
  • 资助金额:
    $ 8.36万
  • 项目类别:
CREATINE KINASE AND ENERGY METABOLISM HOMEOSTASIS
肌酸激酶和能量代谢稳态
  • 批准号:
    2750254
  • 财政年份:
    1995
  • 资助金额:
    $ 8.36万
  • 项目类别:

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